Acute inflammatory responses can result from a wide range of diseases and naturally occurring events such as stroke and myocardial infarction. Common medical procedures can also lead to localized and systemic inflammation. Left untreated inflammation can result in significant tissue loss and may ultimately lead to multi-system failure and death. Interfering with the inflammatory response after injury may be one method to reduce tissue loss. Accumulating evidence supports a major role for the serum innate response or complement system in inflammation.
Recent studies implicate an important role for natural antibody and the classical pathway of complement in the inflammatory response. It has been determined that ischemia-reperfusion injury can be initiated by clonally specific natural IgM that activates the classical pathway of complement. (Zhang et al. (2004) Proc. Natl. Acad. Sci. 101(11):3886-3891.) These studies have led to the identification of pathogenic IgMs and, in turn, the identification of self-peptides that bind natural IgM, described in U.S. Pat. No. 7,442,783. U.S. Pat. No. 7,442,783 describes a conserved region within type II NMHC proteins (corresponding to amino acids 592-603 of Mouse NMHC-IIB (the N2 self-peptide; SEQ ID NO:33)) representing the major epitope for binding of natural IgM following ischmeia in an intestinal model.
Inflammatory diseases or disorders are potentially life-threatening, costly, and affect a large number of people every year. Thus, effective treatments of inflammatory diseases or disorders are needed.